Jingwen Liao

Cell-laden photocrosslinked GelMA–DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering

To effectively repair or replace damaged tissues, it is necessary to design three dimensional (3D) extracellular matrix (ECM) mimicking scaffolds with tunable biomechanical properties close to the desired tissue application. In the present work, gelatin methacrylate (GelMA) and dextran glycidyl methacrylate (DexMA) with tunable mechanical and biological properties were utilized to prepared novel bicomponent polymeric hydrogels by cross-linking polymerization using photoinitiation. We controlled the degree of substitution (DS) of glycidyl methacrylate in DexMA so that they could obtain relevant mechanical properties. The results indicated that copolymer hydrogels demonstrated a lower swelling ratio and higher compressive modulus as compared to the GelMA. Moreover, all of the hydrogels exhibited a honeycomb-like architecture, the pore sizes decreased as DS increased, and NIH-3T3 fibroblasts encapsulated in these hydrogels all exhibited excellent viability. These characteristics suggest a class of photocrosslinkable, tunable mechanically copolymer hydrogels that may find potential application in tissue engineering and regenerative medicine applications.

Reversibly Controlling Preferential Protein Adsorption on Bone Implants by Using an Applied Weak Potential as a Switch

A facile method is needed to control the protein adsorption onto biomaterials, such as, bone implants. Herein we doped taurocholic acid (TCA), an amphiphilic biomolecule, into an array of 1D nano-architectured polypyrrole (NAPPy) on the implants. Doping TCA enabled the implant surface to show reversible wettability between 152° (superhydrophobic, switch-on state) and 55° (hydrophilic, switch-off state) in response to periodically switching two weak electrical potentials (+0.50 and -0.80 V as a switch-on and switch-off potential, respectively). The potential-switchable reversible wettability, arising from the potential-tunable orientation of the hydrophobic and hydrophilic face of TCA, led to potential-switchable preferential adsorption of proteins as well as cell adhesion and spreading. This potential-switchable strategy may open up a new avenue to control the biological activities on the implant surface.

Biomimetic mineralization of anionic gelatin hydrogels: effect of degree of methacrylation

Mineral–polymer composite materials have been used as artificial bone grafts and scaffolds in bone tissue engineering. Polymer-controlled mineralization is effective for fabricating such composites. In this study, we synthesized organic–inorganic composites using anionic gelatin methacrylate (GelMA) hydrogels containing a high percentage of Ca2+ binding-carboxyl groups as a template for mineralization. A homogeneous surface and interior carbonated hydroxyapatite were achieved on the resulting mineralized porous hydrogel composites, and they were confirmed to resemble apatite-like structures. The effect of crosslinker content on mineralization was examined using GelMA hydrogels with different degrees of methylacrylation (DM). It was found that increasing the DM of the hydrogel suppressed the growth of carbonated hydroxyapatite layers, as was evident from the extent of calcification and the morphology of the minerals. The dependency of the mineralization on hydrogel variables was related to the changes in physicochemical properties of gel, including charge density and swelling. Compressive mechanical testing demonstrated that the compressive modulus and strength of the hydrogels increased with increasing DM and mineralization extent. Overall, mineralization of GelMA hydrogels with controllable mineral content and good mechanical properties provides a biomimetic route toward the development of bone substitutes for the next generation of biomaterials. The results of this study also provide insight into better understanding the role of the hydrogel matrix in biomineralization.

Directing Stem Cell Differentiation via Electrochemical Reversible Switching between Nanotubes and Nanotips of Polypyrrole Array

Control of stem cell behaviors at solid biointerfaces is critical for stem-cell-based regeneration and generally achieved by engineering chemical composition, topography, and stiffness. However, the influence of dynamic stimuli at the nanoscale from solid biointerfaces on stem cell fate remains unclear. Herein, we show that electrochemical switching of a polypyrrole (Ppy) array between nanotubes and nanotips can alter surface adhesion, which can strongly influence mechanotransduction activation and guide differentiation of mesenchymal stem cells (MSCs). The Ppy array, prepared via template-free electrochemical polymerization, can be reversibly switched between highly adhesive hydrophobic nanotubes and poorly adhesive hydrophilic nanotips through an electrochemical oxidation/reduction process, resulting in dynamic attachment and detachment to MSCs at the nanoscale. Multicyclic attachment/detachment of the Ppy array to MSCs can activate intracellular mechanotransduction and osteogenic differentiation independent of surface stiffness and chemical induction. This smart surface, permitting transduction of nanoscaled dynamic physical inputs into biological outputs, provides an alternative to classical cell culture substrates for regulating stem cell fate commitment. This study represents a general strategy to explore nanoscaled interactions between stem cells and stimuli-responsive surfaces.

Surface-Dependent Self-Assembly of Conducting Polypyrrole Nanotube Arrays in Template-Free Electrochemical Polymerization

One-dimensional conducting polymer nanostructure arrays could provide short ion transport paths, thus delivering superior chemical/physical performance and having large potential as intelligent switching materials. In this work, in situ electrochemical atomic force microscopy is employed to monitor the self-assembly of conducting polypyrrole nanotube arrays in template-free electrochemical polymerization. The specific spreading behavior of pyrrole micelles on the conductive substrate is important to large-area self-assembly of conducting polypyrrole nanotube arrays and the insight into self-assembly of conducting polypyrrole nanotube arrays is discussed. Moreover, compared with unoriented nanostructured polypyrrole, the conducting polypyrrole nanotube arrays possess enhanced electrical and electrochemical performances.

Nanostructured Conducting Polymers as Intelligent Implant Surface: Fabricated on Biomedical Titanium with a Potential-Induced Reversible Switch in Wettability

Conducting polypyrrole (PPy) nanotube arrays, nanotube networks and irregular films are deposited on biomedical titanium. By in situ application of weak periodic potentials, the nanostructured conducting polymers undergo a reversible switch in wettability, which is a redox process of dopant molecules (as hydrophilic groups) immobilized and de-immobilized on the surface of the conducting polymers.

Taurine-induced fabrication of nano-architectured conducting polypyrrole on biomedical titanium.

In this article, taurine, one of the small biomolecules associated with bone metabolism, is firstly utilized to induce the fabrication of nano-architectured conducting polypyrrole (NCPPy) on biomedical titanium in diverse pH values of phosphate buffer solution (PBS). Accordingly, the possible mechanism for the fabrication of NCPPy is proposed, which is dependent on the states of polytaurine from the polymerization of taurine, i.e., the inability of forming polytaurine and unordered restricted space results in taurine-incorporated and polytaurine-incorporated tightly packed nanoparticles (pH 6.2 and 8.0), respectively, and however, ordered restricted space constructed by polytaurine chains induces the fabrication of polytaurine-incorporated nanopillars (pH 6.8) and polytaurine-incorporated nanowire networks (pH 7.4).

Controlled oxidative nanopatterning of microrough titanium surfaces for improving osteogenic activity

To further enhance the biological properties of acid-etched microrough titanium surfaces, titania nanotextured thin films were produced by simple chemical oxidation, without significantly altering the existing topographical and roughness features. The nanotextured layers on titanium surfaces can be controllably varied by tuning the oxidation duration time. The oxidation treatment significantly reduced water contact angles and increased the surface energy compared to the surfaces prior to oxidation. The murine bone marrow stromal cells (BMSCs) were used to evaluate the bioactivity. In comparison, oxidative nanopatterning of microrough titanium surfaces led to improved attachment and proliferation of BMSCs. The rate of osteoblastic differentiation was also represented by the increased levels of alkaline phosphatase activity and mineral deposition. These data indicated that oxidative nanopatterning enhanced the biological properties of the microrough titanium surfaces by modulating their surface chemistry and nanotopography. Based on the proven mechanical interlocking ability of microtopographies, enhancement of multiple osteoblast functions attained by this oxidative nanopatterning is expected to lead to better implant osseointegration in vivo.

Potential-induced reversible switching in the tubular structure of conducting polypyrrole nanotube arrays

In this article, we report a novel switch property of conducting polypyrrole nanotube arrays (CPNAs) on biomedical titanium, in which the nanotubular structure can be reversibly switched between open and closed states by applying switch-open/close potentials in situ. We propose a new insight into the study of reversible tubular switches in CPNAs.

Chondroitin sulphate-guided construction of polypyrrole nanoarchitectures.

Nanospheres, nanocones, and nanowires are three typical polypyrrole (PPy) nanoarchitectures and electrochemically polymerized with the dope of chondroitin sulphate (CS) in this study. CS, a functional biomacromolecule, guides the formation of PPy nanoarchitectures as the dopant and morphology-directing agent. Combined with our previous reported other PPy nanoarchitectures (such as nanotube arrays and nanowires), this work further proposed the novel mechanism of the construction of PPy/CS nanoarchitectures with the synergistic effect of CS molecular chains structure and the steric hindrance. Compared to the undoped PPy, MC3T3-E1 cells with PPy/CS nanoarchitectures possessed stronger proliferation and osteogenic differentiation capability. This suggests that PPy/CS nanoarchitectures have appropriate biocompatibility. Altogether, the nanoarchitectured PPy/CS may find application in the regeneration of bone defect.